Influenza virus infection (hereinafter, referred to as influenza) caused by influenza virus is frequently a fatal disease. In recent years, viruses such as avian influenza have occurred, which exhibit strong pathogenicity to humans. Avian influenza threatens to be pandemic.
However, drugs applicable to influenza are much fewer than antimicrobial agents or the like. For example, amantadine and oseltamivir currently used have problems such as resistance to them.
A method of using anti-influenza virus agents in combination has been discussed for the purpose of reducing drug resistance of influenza virus, enhancing therapeutic effects, and/or reducing side effects, etc. However, the drugs used in combination are limited in number and do not always produce satisfactory effects.
For example, neuraminidase inhibitors are known as drugs that exhibit effects on influenza virus. Neuraminidase, which is a spike glycoprotein found on the surface of influenza virus, is required for influenza virus infecting cells of the throat or bronchus and proliferating to spread to their neighboring cells. The inhibition of neuraminidase may suppress the spread of such influenza virus to the neighboring cells. For example, a neuraminidase inhibitor oseltamivir is converted to its active form GS-4071 in vivo, which exhibits antiviral effects such that it inhibits neuraminidase on influenza virus (NON-PATENT DOCUMENT 1). Oseltamivir and zanamivir are commercially available as neuraminidase inhibitors. Such drugs have still been developed and studied.
On the other hand, a pyrazine derivative having antiviral activities is known (PATENT DOCUMENT 1). This pyrazine derivative is known to exhibit antiviral effects upon intracellular ribosylphosphorylation such that it inhibits virus RNA polymerase (PATENT DOCUMENT 2).
However, neither a pharmaceutical composition comprising a neuraminidase inhibitor and a pyrazine derivative nor a method of using a neuraminidase inhibitor and a pyrazine derivative in combination has been known so far.    PATENT DOCUMENT 1: Pamphlet of WO00/10569    PATENT DOCUMENT 2: Pamphlet of WO03/015798    NON-PATENT DOCUMENT 1: Japanese Journal of Clinical Medicine, 2003, vol. 61, p. 1975-1979